Genital herpes simplex virus-2 (HSV-2) is among the most common of sexually transmitted diseases in women. Recurrence of latent infection can be frequent. Perinatal fetal transmission results in heightened morbidity and mortality. Current treatment consists of antiviral chemotherapy that merely decreases symptom severity with minimal impact on the incidence of recurrence and transmission rates. Antivirals do not cure. Clinically effective vaccines against HSV-2, a desirable alternative, require parenteral injections, often with unapproved or poorly tolerated adjuvants. This proposal seeks to develop a novel vaginally-applied transmucosal vaccine against genital HSV-2. The proposed vaccine candidate is unique in that it aims to effectively stimulate both humoral and cellular immunity through two components, the cloned HSV-2 gD cDNA and its recombinant gene product, a surface glycoprotein required for viral attachment and infection of the host cell. Manufactured into a novel vaginal suppository delivery vehicle, the efficacy of this vaccine will be tested in animal models of genital HSV-2. Successful results will warrant additional studies to determine tolerance, safety, booster requirements and clinical utility through a larger second phase application. Definitive studies then can be designed to meet the ultimate goal of a well-tolerated, cost-effective improvement in the clinical control of genital HSV-2 as a commercial opportunity. PROPOSED COMMERCIAL APPLICATION Genital herpes simplex virus-2 is among the most common of sexually transmitted diseases in women. Each year, 70,000 new cases of primary infection and 20 million cases of recurrence are reported in the U.S. alone. The current therapy of choice, Acylocvir, is worth over a billion dollars a year. We anticipate that an easily-administered, effective vaccine will be highly profitable.